The Gut and Nonmotor Symptoms in Parkinson's Disease.

Gastrointestinal (GI) symptoms are one of the most common nonmotor symptoms (NMS) in patients with Parkinson's disease (PD) involving the whole GI tract (GIT) and being evident throughout the whole course of the disease. Furthermore, constipation serves as a risk factor for PD as well as an early prodromal NMS of PD. The gut as gateway to the environment with its enteric nervous system (ENS) plays a crucial role in the neurodegenerative process that leads to PD. Alpha-synucleinopathy as the pathological hallmark of PD could be found within the whole GIT in a rostrocaudal gradient interacting with the ENS, the gut microbiome, and enteric glial cells. Bidirectional interactions between the ENS and the central nervous system (CNS) via a brain-gut-enteric microbiota axis have been reported. As well as there is evidence out of animal, autopsy, and epidemiological studies that α-synuclein spreads via rostrocranial transmission by transsynaptic cell-to-cell transfer via the sympathetic and parasympathetic nervous system to the CNS causing the typical neuropathological changes of PD. Recognition of GI NMS as prodromal markers of PD as well as a better understanding of the brain-gut connection offers new insights in the pathophysiology of PD and might provide the opportunity of PD diagnosis before CNS involvement. Hereby the opportunity for development of neuroprotective and disease-modifying therapeutics, respectively, seem to be promising. This chapter covers the variety of GI NMS and its consequences in PD as well as the important role of the gut as part of the pathological process in PD.